School of Chemistry & Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Curr Top Med Chem. 2023;23(20):1952-1963. doi: 10.2174/1568026623666230515145822.
Estrogen-related receptor alpha (ERRα), a member of the nuclear receptor superfamily, is strongly expressed in breast cancer cells. Its overexpression is associated with poor prognosis in triple- negative Breast Cancer (TNBC). ERRα expression could be inhibited by the downregulation of upstream oncogenic growth factors mTOR, HER2, and PI3K. Low expression of ERRα could suppress the migration and angiogenesis of tumor cells by inhibiting the activity of its downstream signals VEGF and WNT11. Studies have confirmed that ERRα inverse agonists can inhibit ERRα expression to treat breast cancer. Inverse agonists of ERRα could disrupt the interactions of ERRα with its coactivators and inhibit tumor development. Existing ERRα inverse agonists have shown moderate efficacy in inhibiting the growth of breast cancer cells. Clinical inverse agonists of ERRα have not been found in the literature. This review focuses on the research progress and the structureactivity relationship of ERRα inverse agonists, providing guidance for the research and discovery of new anti-tumor compounds for TNBC.
雌激素相关受体α（ERRα）是核受体超家族的成员，在乳腺癌细胞中强烈表达。其过表达与三阴性乳腺癌（TNBC）的预后不良相关。ERRα 的表达可以通过下调上游致癌生长因子 mTOR、HER2 和 PI3K 来抑制。ERRα 表达水平低通过抑制其下游信号 VEGF 和 WNT11 的活性来抑制肿瘤细胞的迁移和血管生成。研究已经证实，ERRα 反向激动剂可以通过抑制 ERRα 的表达来治疗乳腺癌。ERRα 的反向激动剂可以破坏 ERRα 与其共激活因子的相互作用，抑制肿瘤的发展。现有的 ERRα 反向激动剂在抑制乳腺癌细胞生长方面表现出中等疗效。文献中尚未发现临床用的 ERRα 反向激动剂。本综述重点介绍了 ERRα 反向激动剂的研究进展和构效关系，为研究和发现用于 TNBC 的新型抗肿瘤化合物提供了指导。
